Abstract
BackgroundRetroviruses encode a very limited number of proteins and therefore must exploit a wide variety of host proteins for completion of their lifecycle.MethodsWe performed an insertional mutagenesis screen to identify novel cellular regulators of retroviral replication.ResultsThis approach identified the ATP-dependent chromatin remodeler, chromodomain helicase DNA-binding protein 2 (CHD2), as well as the highly related CHD1 protein, as positive regulators of both MLV and HIV-1 replication in rodent and human cells. RNAi knockdown of either CHD2 or the related CHD1 protein, in human cells resulted in a block to infection by HIV-1, specifically at the level of transcription.ConclusionsThese results demonstrate that CHD1 and CHD2 can act as positive regulators of HIV-1 gene expression.
Highlights
Retroviruses encode a very limited number of proteins and must exploit a wide variety of host proteins for completion of their lifecycle
The mutant CHO-K1 cell lines display resistance to infection by both MLV and HIV-1 To determine if the defect in the 6/B-6 and 6/B-7 mutant cell lines was specific to MLV or if it affects HIV-1 infection, wild type CHO-K1 cells and mutant cell lines were seeded in 96 well plates and challenged with either a VSV-G pseudotyped MLV reporter virus VGIP-Luc [VSV-G] or a VSV-G pseudotyped HIV-1 reporter virus pNL43-Luc-R+E− [VSV-G] encoding luciferase
Cell viability was not affected under these conditions. These results demonstrate that CHD1 and chromodomain helicase DNA-binding protein 2 (CHD2) are positive regulators of HIV-1 gene expression in human cells
Summary
Retroviruses encode a very limited number of proteins and must exploit a wide variety of host proteins for completion of their lifecycle. Retroviruses cause a wide range of diseases in humans and animals, including cancer (HTLV-1, and HTLV-2) and AIDS (HIV-1 and HIV-2) in humans These viruses exploit a large number of cellular proteins and other factors to facilitate different steps of virus replication. A number of comprehensive genetic screens, most relying on RNAi-knockdown technology, have revealed a number of cellular factors that are important for replication by retroviruses such as HIV-1 [1,2,3,4] While this is a powerful approach, its impact is limited by the fact that the RNAi-knockdown level seen with individual genes is often incomplete, i.e. expression of the target gene is reduced but is not completely ablated.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
